On June 12, 2014, Rancati, Fabio; Linney, Ian; Knight, Chris; Schmidt, Wolfgang published a patent.Synthetic Route of 124038-36-4 The title of the patent was Preparation of compounds having muscarinic receptor antagonist and beta2 adrenergic receptor agonist activity. And the patent contained the following:
The present invention relates to compounds I [wherein: Q is a group of formula Q1, Q2 and Q3; Z is H or OH; Y is selected from A1B(CH2)n1A2CD(CH2)mE and A1CBC’D(CH2)pE, which are divalent groups; wherein A1 and A2 are independently absent or are selected from the group consisting of C1-6-alkylene, C3-8-cycloalkylene and C3-8-heterocycloalkylene optionally substituted by one or more substituents selected from the group consisting of C1-6-alkyl, aryl-(C1-6-alkyl) and heteroaryl-(C1-6-alkyl);]. [B is absent or is selected from the group consisting of C3-8-cycloalkylene, C3-8-heterocycloalkylene, arylene and heteroarylene, optionally substituted by one or more groups selected from halogens, CN, linear or branched C1-6-alkyl, linear or branched C1-6-haloalkyl, C1-6-alkoxy, aryl, aryl-(C1-6-alkyl), NR7R8 and heteroaryl;C and C’ are absent or are independently selected from the group consisting of oxygen, C(:O), OC(:O) and -C(OO)- or one of the following:]. [NR7C(:O), O(CH2)nO2C, N((CH2)nCO2R7)SO2, NR7(CH2)nO2C, CO2(CH2)nNR7C(:O), N(COR7)(CH2)nO2C, O2CCR7R8NHC(:O), NR7CONR7′(CH2)nO2C, C(:O)NR7(CH2)nO2C, (CH2)O2C, SO2NR7(CH2)nO2C, C12, N(SO2R7)(CH2)nO2C, C14; wherein R7, R7′ and R8 are independently H or selected from the group consisting of linear or branched C1-6-alkyl, C3-8-cycloalkyl, (C3-8-cycloalkyl)-(C1-6-alkyl), (C3-8-heterocycloalkyl)-(C1-6-alkyl), aryl and aryl-(C1-6-alkyl), optionally substituted by one or more substituents selected from the group consisting of C1-6-alkyl, C1-6-haloalkyl, halogen atoms, C1-6-alkoxy and C1-6-alkoxy;]. [D is absent or is selected from the group consisting of C1-6-alkylene, arylene, heteroarylene and C3-8-heterocycloalkylene, optionally substituted by one or more C1-6-alkyl groups; n, n’, m and p are independently O or an integer from 1 to 3; E is absent or is selected from O and OC(:O); G is arylene optionally substituted by one or more substituents selected from the group consisting of halogen atoms, OH, oxo (:O), SH, NO2, CN and NH2;]. [R1 and R2 are independently H or selected from the group consisting of C1-6-alkyl and aryl, optionally substituted by one or more halogen atoms; M is NR3; R3 is H or C1-6-alkyl; R4 is a group of formula J1] acting both as muscarinic receptor antagonists and beta2 adrenergic receptor agonists. Thus, 8-hydroxyquinolin-2-one derivative II was prepared from 3-hydroxybenzophenone via reductive amination with formamide; hydrolysis with HCl in MeOH; N-alkoxycarbonylation with di(tert-butyl) dicarbonate in CH2Cl2 containing EtN(CHMe2)2 followed by treatment with K2CO3 in MeOH; chromatog. resolution with CHIRALPAK® AD; etherification with 4-BrCH2C6H4CO2Me in MeCN containing K2CO3; hydrolysis with HCl in dioxane/MeOH; alkoxycarbonylation with (R)-quinuclidin-3-yl chloroformate (III) in pyridine;. Saponification with aqueous LiOH in THF; amidation with 3-(1,3-dioxolan-2-yl)propyl piperidine-4-carboxylate hydrochloride (IV·HCl) in DMF containing EtN(CHMe2)2 and HATU; deacetalation with aqueous HCl in THF; and reductive amination with of (R)-5-(2-amino-1-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one hydrochloride (V·HCl) in MeOH containing NaBH(OAc)3 and AcOH. The present invention also relates to processes for their preparation, to compositions comprising them, to therapeutic uses and combinations with other pharmaceutical active ingredients. The receptor activity of I was determined [the Ki values (calculated from IC50 values by the Cheng and Prusoff equation) of most of the compounds of the examples are less than 10 nM in the M3 Receptor and in the β2 adrenoceptor radioligand binding assays]. The experimental process involved the reaction of Methyl 3-(1,3-dioxolan-2-yl)benzoate(cas: 124038-36-4).Synthetic Route of 124038-36-4
The Article related to muscarinic receptor antagonist, beta2 adrenergic receptor agonist, Alkaloids: Alkaloids Containing One Nitrogen Atom At A Bridgehead and other aspects.Synthetic Route of 124038-36-4
Referemce:
1,3-Benzodioxole – Wikipedia,
Dioxole | C3H4O2 – PubChem